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Biomedical subjects

A Franke

Publications and source records attributed to A Franke.

At least 109 records · Page 6Linked to original sources

Enumeration of CD34-positive hematopoietic progenitor cells by flow cytometry: comparison of a volumetric assay and the ISHAGE gating strategy.

In order to optimize peripheral blood stem cell (PBSC) collection for transplantation, absolute CD34 counts are necessary to determine the exact time-point for sufficient leukapheresis. In an effort to establish and to validate a rapid and reproducible assay for PBSC enumeration, different recommendations for selection of monoclonal antibodies, lysis techniques, analysis parameters and gating strategies were developed. In this methodical study, two gating strategies for PBSC enumeration were compared, in order to validate the accuracy of PBSC counting in peripheral blood and apheresis products. Gating strategy I was performed using volumetric flow cytometry and reference beads whereas gating strategy II was done according to the ISHAGE guidelines. The highly standardized volumetric assay seems to be superior to the more 'expert-reliant' ISHAGE procedure requiring more 'manual work' by the cytometrist.

Antigens, CD34↗

Influence of body position on defibrillation thresholds of nonthoracotomy implantable defibrillators: a prospective randomized evaluation.

INTRODUCTION: Defibrillation thresholds (DFTs) usually are determined with the patient in the supine position. However, patients may be in the upright position when a shock is delivered during follow-up, which may explain some first shock failures observed clinically. This study investigated whether body posture affects defibrillation energy requirements of nonthoracotomy implantable cardioverter defibrillators with biphasic shocks. METHODS AND RESULTS: Using a step up-down protocol, DFTs were compared intraindividually in 52 patients ("active-can" sytems in 41 patients, two-lead systems in 11 patients) for the supine and upright positions as achieved by a tilt table. The mean DFT was 7.3 +/- 4.2 J in the supine versus 9.2 +/- 4.8 J in the upright position (P = 0.002). Repeated comparison in reversed order 3 months after implantation in 22 patients revealed thresholds of 6.2 +/- 2.5 J (supine) versus 8.4 +/- 3.7 J (upright; P < 0.03) 1 week and 4.4 +/- 2.4 J (supine) versus 6.2 +/- 4.1 J (upright; P < 0.04) 3 months after implantation. DFTs decreased significantly for both body positions from 1 week to 3 months after implantation (P < 0.04). CONCLUSION: (1) DFTs for biphasic shocks delivered by nonthoracotomy defibrillators are higher in the upright compared to the supine body position. (2) Differences remain significant 3 months after implantation. For both body positions, DFT decreases significantly from 1 week to 3 months after implantation. These findings have important implications for programming first shock energy to lower than maximal values or for development of devices with lower maximal stored energy.

Defibrillators, Implantable↗

[Therapy of febrile neutropenia episodes in systemic hematologic illnesses with new once daily ceftriaxone administration].

In this open label prospective multicenter trial, 420 patients with neutropenia < 1000/microliter, fever > 38.5 degrees C and hematological malignancies were treated with ceftriaxone. Acute leukemia (n = 238) and high-grade lymphoma patients (n = 182) from 35 centers were enrolled. Between February 1992 and January 1996, patients were treated with 2 g ceftriaxone i.v. per day either as monotherapy (n = 135), or in combination with aminoglycosides (n = 235), glycopeptides (n = 37), or other antimicrobial agents (n = 13). Patients' median age was 54 years (range 15 to 97) with a median Karnofsky-performance-score of 6.0. The median neutrophil counts were 400/microliter. Fever was of unknown origin (FUO) in 268 (63.8%) of patients. Clinically defined infections (CDI) were diagnosed in 152 (36.2%) cases, including 74 (17.8%) episodes with pneumonia. Response to the initial approach with ceftriaxone was observed in 56.2% of febrile episodes, including 93 (68.8%) treatment courses with ceftriaxone alone. Concerning defervescence of fever ceftriaxone monotherapy was successful as compared to ceftriaxone in combination. Analysis revealed a low risk characterized by higher neutrophil counts (> or = 500/microliter; p < 0.0001), better Karnofsky-performance-score (> or = 7; p = 0.01), duration of neutropenia (< or = 5 days; p = 0.008) from start of antimicrobial treatment and duration of neutropenia per cycle (< or = 10 days; p = 0.0016). At the end of the observation, an overall response was obtained in 88.3% of the patients (n = 371) without statistical difference between patients treated with ceftriaxone alone or in combination. Once daily ceftriaxone either alone or in combination was effective in patients with hematological malignancies. Monotherapy was effective in a low risk group characterized by neutrophil counts (> or = 500/microliter), a Karnofsky-performance-score (> or = 7) and a duration of neutropenia (< or = 5 days) at the commencement of treatment.

Acute Disease↗

[High dosage chemotherapy and peripheral blood stem cell transplantation in breast carcinoma].

Chemotherapeutic agents have been shown experimentally to have a dose-response relationship in drug-sensitive cancer. This suggests that high-dose chemotherapy (HDC) might improve the therapeutic outcome in breast cancer. The emergence of modern supportive measures like peripheral blood stem cell rescue has significantly decreased the toxicity and cost of HDC. HDC is being employed for patients with metastatic and high-risk breast cancer (> 10 involved axillary lymph nodes). Randomized phase III trials are urgently needed. At the moment patient with breast cancer should only be treated with HDC in context with a clinical trial.

Antineoplastic Combined Chemotherapy Protocols↗

The association of plasma micronutrients with the risk of cervical dysplasia in Hawaii.

Limited data from hematological studies suggest that certain nutrients, including carotenoids, tocopherols, and vitamin C, may protect against malignant change in cervical tissue. Recognizing that human papillomavirus (HPV) infection induces most neoplastic transformation of cervical tissue, the authors conducted a case-control study to examine the association of plasma micronutrient concentrations with the risk of cervical dysplasia after careful adjustment for HPV infection, using a sensitive and reliable HPV detection method. The sample included 147 multiethnic women, between 18 and 65 years of age, with biopsy-confirmed squamous intraepithelial lesions (SILs) of the cervix and 191 clinic controls identified between 1992 and 1996. Cases were identified through cytology and pathology logs in three clinics on Oahu, Hawaii. Controls were selected randomly from admission logs of the participating clinics. In-person interviews were conducted in the subjects' homes, and a fasting blood sample was drawn to measure plasma levels of lutein, lycopene, cryptoxanthin, total carotene, retinol, tocopherol, ascorbic acid, and cholesterol. The presence and type of HPV was determined in exfoliated cell samples using PCR dot blot hybridization. Mean plasma lycopene, total cryptoxanthin, and alpha-cryptoxanthin levels were lower among cases than controls. We found an inverse dose-response of alpha-cryptoxanthin, total tocopherol, and alpha-tocopherol to the odds ratios for cervical SIL after adjustment for HPV and other confounders. The odds ratio among women in the highest compared with the lowest quartile was 0.3 (95% confidence interval, 0.1-0.7) for alpha-cryptoxanthin and 0.3 (95% confidence interval, 0.1-0.8) for alpha-tocopherol. Negative trends in the odds ratios were suggested for other carotenoids and vitamin C, but these were weak, and confidence intervals were wide. Our results support existing evidence that high plasma levels of antioxidants may reduce the risk of cervical SILs independent of HPV infection. These findings are significant because diet is potentially modifiable, and nutrition education and dietary intervention might be targeted at specific high-risk groups.

Adolescent↗

Cellular immunity and immunotherapy against deoxyribonucleic acid virus-induced tumors.

An important role in the immune defense against deoxyribonucleic acid virus induced tumors is mediated by T-cells, as is evident from aetiological, animal model, and clinical data. In this review the most recent observations in this field are described for three prominent members of this family of viruses, namely human papillomavirus associated with human cervical cancer, human adenovirus associated with lung infections in humans and tumors in rodents, and simian virus 40 associated with rodent tumors and human mesothelioma, osteosarcoma and ependymoma.

Animals↗

Quantitative analysis of the morphology of secundum-type atrial septal defects and their dynamic change using transesophageal three-dimensional echocardiography.

BACKGROUND: A noninvasive method for the determination of size and spatial relationships of atrial septal defects to adjacent cardiac structures, which would be advantageous to those contemplating device closure, is described. The aim of the study was to examine the value of transesophageal three-dimensional echocardiography for this purpose. METHODS AND RESULTS: Three-dimensional reconstruction of transesophageal two-dimensional echocardiography was performed in 17 patients. Left-to-right shunt (by oximetry in 16 of 17 patients) was 2.4 to 16.2 L/min, and the Qp/QS ratio was 1.4 to 4.7. The defect area of the atrial septal defect was measured throughout the whole cardiac cycle each 40 ms from the three-dimensional data set. Results were compared with shunt parameters by oximetry and with intraoperative measurements. Distances between atrial septal defect and mitral and tricuspid annulus and the orifices of the caval and pulmonary veins were also measured. The atrial septal defect area ranged from 0.2 to 2.4 cm2 (diastole) to 0.5 to 5.6 cm2 (systole). The maximal area at end-systole was 108% of the area at beginning of systole, and the minimal area at end-diastole was 43%. The defect area correlated significantly with the Qp/QS ratio (r=.70), and the maximal atrial septal defect diameters as measured by using three-dimensional echocardiography correlated well with intraoperative measurements (r=.87). Distances to mitral and tricuspid annulus and to the superior caval vein were determined in all patients. Distances to orifice of the inferior caval vein were measured in 12 patients, and orifices of right pulmonary veins were visible in 5 patients. CONCLUSIONS: Transesophageal three-dimensional echocardiography of atrial septal defects allows the determination of the instantaneous defect area and its dynamic changes and thus provides valuable information about the distances to adjacent cardiac structures. This may have clinical implications for the selection of patients suitable for interventional closure and for the assessment of procedural success.

Adult↗

Prognostic significance of dysplastic features of hematopoiesis in patients with de novo acute myelogenous leukemia.

The detection of dysplastic features of hematopoiesis in de novo acute myeloid leukemia (AML) by light microscopy is defined as AML with trilineage myelodysplasia (AML/TLMD). The prognostic relevance of these dysplastic features for patients with de novo AML remains unclear. In order to evaluate the role of dysplasia in de novo AML, bone marrow aspirates from 69 patients were analyzed prospectively and investigated separately for erythropoiesis, granulopoiesis and megakaryopoiesis by three independent investigators. The overall complete remission (CR) rate was 48.8% and partial remission (PR) or nonresponders constituted 52.2% of the patients investigated. The median overall survival time was 5 months with a disease-free interval of 3.5 months for all patients. Dysgranulopoiesis (DysG) was observed in 30.4%, dysmegakaryopoiesis (DysM) in 50.7%, and dyserythropoiesis (DysE) in 43.5%. Of all patients, 26.0% showed trilineage dysplastic features and were thus classified as AML/TLMD. A significantly worse prognosis (Kaplan-Meyer plot, Student's t-test) was calculated for those patients with detection of only DysG (p = 0.002), DysM (p = 0.02), DysE (p = 0.04) as compared with patients without any dysplastic signs. An unfavorable karyotype was correlated with patients showing DysG (P = 0.02) and DysM (P = 0.04). For these patients with an unfavorable karyotype, the occurrence of any dysplastic features had no additional prognostic impact. Dysplastic features (DysG, DysM, DysE) seem to be an important prognostic factor in de novo AML correlating with short overall survival. DysG and DysM correlated well with the appearance of unfavorable chromosomal abnormalities. It may be reasonable to assume that patients with dysplastic features should be considered for more aggressive treatment schedules at the time of diagnosis.

Adolescent↗

[3-D echocardiography: technical toy in search of a clinical application or logical evolution of diagnostic equipment?].

In recent years, 3D echocardiographic reconstruction and real time 3D echocardiography have been developed. Reconstruction techniques are based on one of two principles: acoustic or electromagnetic location devices that identify the spatial position of the transducer during imaging, or transducers that image from a fixed position varying the sector orientation in a predefined way. Animated, dynamic reconstructions of cardiac structures are possible, and the 3D data set can be sliced and viewed in any desired way after acquisition. The mitral annulus and congenital malformations of the heart have been imaged and studied successfully by 3D echo. Mass and volume calculations based on 3D data sets have been shown to be extraordinarily accurate by several investigators working with different techniques. Since the 3D data set is more comprehensive than any set of 2D images, such calculations are fundamentally superior to 2D or M-mode derived parameters. Color Doppler data can also be reconstructed into 3D data sets, with possible applications to proximal convergence zone calculations. However, broad implementation of 3D echo in clinical practice is hampered to date by cumbersome manual tracing to derive quantitative parameters and sometimes by insufficient image quality. Nevertheless, the rapid technical evolution, now including real-time 3D echo, ensures an important role for 3D echo in future echocardiography.

Cardiac Volume↗

[Transesophageal Doppler echocardiography assessment of mitral valve insufficiency: Comparison of jet area, pulmonary venous flow profile, proximal jet diameter, maximal regurgitation flow rate and regurgitation orifice area with angiography].

UNLABELLED: In transesophageal echocardiography several methods have been used to grade mitral regurgitation. For a direct comparison of these techniques, 36 patients (60 +/- 13 years) with native mitral regurgitation underwent multiplane transesophageal echocardiography and angiography within 5 days. We compared the following measurements: 1) The maximal color jet area of mitral regurgitation, 2) the ratio of maximal systolic to diastolic pulmonary venous flow velocity in the left upper pulmonary vein, 3) the proximal jet width of mitral regurgitation, 4) the maximal regurgitant flow rate Qmax, measured by the proximal convergence method, 5) the regurgitant office area Areg, calculated by dividing Qmax by maximal regurgitant velocity obtained by continuous wave Doppler. RESULTS: The correlation between color jet area (r = 0.4; p < 0.05) or pulmonary venous flow (r = -0.3; p = n.s.) with angiographic severity of mitral regurgitation is low. The sensitivity of the retrospective best cut-off values is 69% (color jet area) and 83% (pulmonary venous flow). Using retrospective best cut-off values all patients with mitral regurgitation Sellers grade III and IV are correctly identified by a proximal jet width > or = 0.7 cm, Qmax > or = 300 ml/s or a Areg > or = 0.5 cm2 (sensitivity and specificity of 83-100%). Spearman's rank coefficient demonstrated a high correlation (r = 0.75-0.77; p < 0.001) between proximal jet width, Qmax and Areg and with angiographic severity. CONCLUSION: Multiplane transesophageal echocardiographic grading of mitral regurgitation by proximal jet width or proximal convergence zone shows comparably good results and is clearly superior to grading by color jet area or pulmonary venous flow, if adequate image quality is achieved.

Adult↗

Determination of left ventricular mass and circumferential wall thickness by three-dimensional reconstruction: in vitro validation of a new method that uses a multiplane transesophageal transducer.

Elevated left ventricular mass and increased wall thickness have important prognostic implications in clinical medicine. However, these parameters have been incompletely characterized by one- and two-dimensional echocardiography. Therefore this study was performed to validate in vitro measurement of left ventricular mass and circumferential wall thickness with a multiplane transesophageal transducer and three-dimensional reconstruction. Results for mass measurements were also compared with a standard method for the determination of left ventricular mass, the Penn convention. Fourteen necropsied left ventricles were scanned in a water bath by a volume-rendering, three-dimensional reconstruction system. There was an excellent correlation and high agreement for determination of three-dimensional left ventricular mass (r = 0.98; standard error of the estimate [SEE] = 9.6 gm; y = 1.02x + 0.46) and wall thickness (r = 0.93; SEE = 1.4 mm; y = 0.95x + 1.64) compared with anatomic measurements. Left ventricular mass by a simulated Penn convention revealed a lower correlation and larger error compared with three-dimensional measurements (r = 0.72; SEE = 42.8 gm; y = 1.01x + 9.61). Therefore determination of left ventricular mass by three-dimensional reconstruction was validated in vitro and was superior to one-dimensional echocardiographic methods.

Algorithms↗

Interventional atrioseptostomy by application of monopolar high-frequency alternating current. In vitro evaluation of a new device.

RATIONALE AND OBJECTIVES: The authors evaluate the use of a new device for interventional creation of atrial septal defects (ASD) working with high-frequency alternating current in an in vitro study with porcine atria. METHODS: The device consists of a symmetrical cage of six superelastic monofile wires, including a microthermistor that is placed via a catheter into a punctured hole in the porcine foramen ovale. The device is used as a differential electrode for monopolar, temperature-controlled application of high-frequency alternating current for thermal modelling of ASD. RESULTS: Application of current for 60 seconds caused temperature-dependent, sized ASDs. CONCLUSION: In vivo animal studies to evaluate possible side effects and long term patency of the ASDs are justified and warranted.

Animals↗

The dosage compensation system of Drosophila is co-opted by newly evolved X chromosomes.

In species where males and females differ in number of sex chromosomes, the expression of sex-linked genes is equalized by a process known as dosage compensation. In Drosophila melanogaster, dosage compensation is mediated by the binding of the products of the male-specific lethal (msl) genes to the single male X chromosome. Here we report that the sex- and chromosome-specific binding of three of the msl proteins (MSLs) occurs in other drosophilid species, spanning four genera. Moreover, we show that MSL binding correlates with the evolution of the sex chromosomes: in species that have acquired a second X chromosome arm because of an X-autosome translocation, we observe binding of the MSLs to the 'new' (previously autosomal) arm of the X chromosome, only when its homologue has degenerated. Moreover, in Drosophila miranda, a Y-autosome translocation has produced a new X chromosome (called neo-X), only some regions of which are dosage compensated. In this neo-X chromosome, the pattern of MSL binding correlates with the known pattern of dosage compensation.

Animals↗

Phylogenetic analysis of hepatitis C virus isolates and their correlation to viremia, liver function tests, and histology.

Nucleotide sequence analysis of hepatitis C virus (HCV) strains showed substantial variability leading to a classification into several genotypes and subtypes. The data correlating HCV genotypes and subtypes with hepatitis C viremia levels, demographic characteristics of patients (age, mode of transmission, duration of infection), and severity of liver disease are conflicting. The interpretation of several studies is further complicated because the molecular methods used lacked specificity for genotyping/subtyping and underestimated viremia levels, especially in patients infected with HCV genotypes 2 and 3. In the present study we investigated 97 consecutive patients with chronic hepatitis C using molecular "gold standard" methods. HCV subtyping was performed by sequence and phylogenetic analysis of the nonstructural (NS)-5 region and serum HCV-RNA concentration was assessed by a validated genotype-independent quantitative reverse-transcription-polymerase chain reaction assay using an internal RNA standard. Patients infected with subtypes HCV-1b, HCV-2a-c, and HCV-4 were older than patients infected with HCV-1a and HCV-3a. Serum HCV-RNA levels ranged from 1.5 x 10(4) to 1.0 x 10(8) copies/mL with no significant differences between median serum HCV-RNA concentrations in patients infected with different genotypes/subtypes. Although patients infected with HCV-1b were older, no biochemical or histological evidence was obtained that this subtype is associated with more severe liver disease. Furthermore, the present study showed a lack of correlation between the serum HCV-RNA concentration, biochemical parameters, and liver histology. The median serum HCV-RNA levels in patients with chronic persistent hepatitis, chronic active hepatitis, and liver cirrhosis were 5.0 x 10(6) copies/mL, 2.5 x 10(6) copies/mL, and 5.0 x 10(6) copies/mL, respectively. These differences were not significant. In conclusion, using optimized and validated molecular techniques, the present cross-sectional study showed no correlation between HCV genotypes/subtypes, viremia, liver function test results, and histology.

Adult↗

Phylogenetic analysis of hepatitis C virus isolates from hemodialysis patients.

A high prevalence of hepatitis C virus (HCV) infection has been reported in hemodialysis patients. Main risk factors for transmission are previous blood transfusions and possibly nosocomial infections within the dialytic environment. In the present study 224 hemodialysis patients from the same department were tested for the presence of anti-HCV antibodies and HCV-RNA. The presence of anti-HCV in hemodialysis patients was correlated with a history of more than 10 blood transfusions (P = 0.001) and with a duration of hemodialysis treatment for more than 10 years (P = 0.001). The issue of possible patient-to-patient infection was addressed by sequence analysis of all HCV-RNA positive hemodialysis patients (N = 14) together with a control panel of HCV isolates from 56 unrelated non-hemodialysis patients with hepatitis C from the same geographical area. Subsequent phylogenetic analysis of nucleotide sequences obtained from the 5'-noncoding region and the nonstructural NS-5 region of the HCV genome revealed that only two hemodialysis patients were infected by a highly related HCV isolate. The remaining HCV-RNA positive hemodialysis patients including those without previous blood transfusions were all infected by phylogenetically-distant HCV isolates, providing evidence against a nosocomial transmission route. The data of the present study show that molecular epidemiological techniques are important to investigate the issue of nosocomial infection. In our hemodialysis unit patient-to-patient infection appears uncommon and draws attention towards other possible (such as, blood products such as human serum albumin, immunoglobulins) or even yet unrecognized transmission routes.

Adult↗